ArticleThe Journal of biological chemistry2010
Real-time NMR study of guanine nucleotide exchange and activation of RhoA by PDZ-RhoGEF.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 45 citations in OpenAlex.
- Optogenetic control of a GEF of RhoA uncovers a signaling switch from retraction to protrusion.eLife · 2025Article
- Structural Dynamics of Rho GTPases.Journal of molecular biology · 2025Review
- ExploitingJournal of the American Chemical Society · 2025Article
- Tumor-derived RHOA mutants interact with effectors in the GDP-bound state.Nature communications · 2024Article
- Tankyrase regulates epithelial lumen formation via suppression of Rab11 GEFs.The Journal of cell biology · 2021Article
- Structure of an inactive conformation of GTP-bound RhoA GTPase.Structure (London, England : 1993) · 2021Article
- Neuropathy-causing TRPV4 mutations disrupt TRPV4-RhoA interactions and impair neurite extension.Nature communications · 2021Article
- Structural Design and Analysis of the RHOA-ARHGEF1 Binding Mode: Challenges and Applications for Protein-Protein Interface Prediction.Frontiers in molecular biosciences · 2021Article
- Dynamic studies of H-Ras•GTPγS interactions with nucleotide exchange factor Sos reveal a transient ternary complex formation in solution.Scientific reports · 2016Article
- Fn14 is regulated via the RhoA pathway and mediates nuclear factor-kappaB activation by Angiotensin II.American journal of translational research · 2016Article
- Characterization of Early Enzymes Involved in TDP-Aminodideoxypentose Biosynthesis en Route to Indolocarbazole AT2433.Chembiochem : a European journal of chemical biology · 2015Article
- Structural insights into the activation of the RhoA GTPase by the lymphoid blast crisis (Lbc) oncoprotein.The Journal of biological chemistry · 2014Article
- A general NMR-based strategy for the in situ characterization of sugar-nucleotide-dependent biosynthetic pathways.Organic letters · 2014Article
- Inhibition of farnesyl pyrophosphate synthase prevents angiotensin II-induced cardiac fibrosis in vitro.Clinical and experimental immunology · 2014Article
- Automated NMR fragment based screening identified a novel interface blocker to the LARG/RhoA complex.PloS one · 2014Article
- A bacterial toxin catalyzing tyrosine glycosylation of Rho and deamidation of Gq and Gi proteins.Nature structural & molecular biology · 2013Article
- A Salmonella typhimurium-translocated glycerophospholipid:cholesterol acyltransferase promotes virulence by binding to the RhoA protein switch regions.The Journal of biological chemistry · 2012Article
- Optimization and stabilization of Rho small GTPase proteins for solution NMR studies: The case of Rnd1.Small GTPases · 2011Article
- Mechanistic insights into specificity, activity, and regulatory elements of the regulator of G-protein signaling (RGS)-containing Rho-specific guanine nucleotide exchange factors (GEFs) p115, PDZ-RhoGEF (PRG), and leukemia-associated RhoGEF (LARG).The Journal of biological chemistry · 2011Article
- Insight into the role of dynamics in the conformational switch of the small GTP-binding protein Arf1.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small guanosine triphosphatases (GTPases) become activated when GDP is replaced by GTP at the highly conserved nucleotide binding site. This process is intrinsically very slow in most GTPases but is significantly accelerated by guanine nucleotide exchange factors (GEFs). Nucleotide exchange in small GTPases has been widely studied using spectroscopy with fluorescently tagged nucleotides. However, this method suffers from effects of the bulky fluorescent moiety covalently attached to the nucleotide. Here, we have used a newly developed real-time NMR-based assay to monitor small GTPase RhoA nucleotide exchange by probing the RhoA conformation. We compared RhoA nucleotide exchange from GDP to GTP and GTP analogues in the absence and presence of the catalytic DH-PH domain of PDZ-RhoGEF (DH-PH(PRG)). Using the non-hydrolyzable analogue guanosine-5'-O-(3-thiotriphosphate), which we found to be a reliable mimic of GTP, we obtained an intrinsic nucleotide exchange rate of 5.5 x 10(-4) min(-1). This reaction is markedly accelerated to 1179 x 10(-4) min(-1) in the presence of DH-PH(PRG) at a ratio of 1:8,000 relative to RhoA. Mutagenesis studies confirmed the importance of Arg-868 near a conserved region (CR3) of the Dbl homology (DH) domain and revealed that Glu-741 in CR1 is critical for full activity of DH-PH(PRG), together suggesting that the catalytic mechanism of PDZ-RhoGEF is similar to Tiam1. Mutation of the single RhoA (E97A) residue that contacts the pleckstrin homology (PH) domain rendered the mutant 10-fold less sensitive to the activity of DH-PH(PRG). Interestingly, this mutation does not affect RhoA activation by leukemia-associated RhoGEF (LARG), indicating that the PH domains of these two homologous GEFs may play different roles.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.